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1 ty of the bovine bc1 complex (Ki = 80 nm) to atovaquone.
2 erential sensitivity of these two species to atovaquone.
3 e bc(1) complexes resistant to inhibition by atovaquone.
4 or this study we focus on the anti-malarial, atovaquone.
5 new antimalarial agents: 5-fluoroorotate and atovaquone.
6 line and a broad spectrum antiparasitic drug atovaquone.
7 an endochin-like quinolone (ELQ) prodrug and atovaquone.
8 fected patients receiving treatment doses of atovaquone.
9 to established antimalarials chloroquine and atovaquone.
10 ng clinical isolates harboring resistance to atovaquone.
11 cross-resistance with the antimalarial drug atovaquone.
12 that are resistant to the anti-malarial drug atovaquone.
13 intaining little to no cross-resistance with atovaquone.
14 sensitivity of the cytochrome bc1 complex to atovaquone.
15 ve either enhanced or reduced sensitivity to atovaquone.
16 developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compare
17 mg twice daily (BID) for 14 days followed by atovaquone 1500 mg BID for 14 days, or vice-versa, with
18 open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100
19 0 subjects receiving EFV in combination with atovaquone 750 mg BID achieved an atovaquone C avg>18.5
20 ggest that the currently recommended dose of atovaquone 750 mg BID for treatment of mild to moderate
21 of 10 subjects receiving EFV-based cART plus atovaquone 750 mg BID had an atovaquone C avg>15 microg/
23 The subjects were assigned to receive either atovaquone (750 mg every 12 hours) and azithromycin (500
25 roximately 200 fold) than that observed with atovaquone, a licensed bc(1)-specific antimalarial drug.
26 t parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of d
29 etermine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic su
30 llowing dose regimens: (1) 250 milligrams of atovaquone and 100 milligrams of proguanil (250/100 mill
31 milligrams on day -7, (4) 500 milligrams of atovaquone and 200 milligrams of proguanil (500/200 mill
32 igrams) on day -7 or, (5) 1000 milligrams of atovaquone and 400 milligrams of proguanil (1000/400 mil
33 with this protocol, such as the antimalarial Atovaquone and antitheilerial Parvaquone, thus evidencin
36 therapy in 65 percent of those who received atovaquone and azithromycin and 73 percent of those who
37 or the treatment of babesiosis, a regimen of atovaquone and azithromycin is as effective as a regimen
40 d by 15 percent of the subjects who received atovaquone and azithromycin, as compared with 72 percent
42 nnot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the p
43 ith chloroquine resistance, a combination of atovaquone and proguanil or quinine plus tetracycline or
46 ation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confiden
48 l antimalarial agents acquired resistance to atovaquone at high frequency, but not to 5-fluoroorotate
50 Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted
51 ceiving EFV-based cART had 47% and 44% lower atovaquone AUCtau than subjects not receiving cART at at
52 dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg
54 of the changes in cytochrome b structure and atovaquone binding with the mutated bc(1) complexes prov
55 of the amino acid side-chains may determine atovaquone-binding affinity, and thereby selective toxic
56 e, including amino acid substitutions in the atovaquone-binding regions of cytochrome b (cytb) and th
57 ovide the first molecular description of how atovaquone binds to the bc1 complex and explain the diff
60 based cART plus atovaquone 750 mg BID had an atovaquone C avg>15 microg/mL, which has previously been
61 ation with atovaquone 750 mg BID achieved an atovaquone C avg>18.5 microg/mL, a concentration that ha
62 que metabolic signatures were also found for atovaquone, chloroquine, proguanil, cycloguanil and meth
64 ge for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human ba
65 in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=
66 ructural basis for the selective toxicity of atovaquone could help in designing drugs against infecti
68 me b, the sensitivity of the yeast enzyme to atovaquone decreased (Ki = 100 nm) with no loss in activ
69 e AUCtau than subjects not receiving cART at atovaquone doses of 750 mg BID and 1500 mg BID, respecti
72 re common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of th
75 ng on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2
76 c stem cell transplantation, extended use of atovaquone for Pneumocystis prophylaxis was associated w
80 ant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocyst
81 val of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of
85 utinely achieved clinically in human plasma, atovaquone inhibits STAT3 phosphorylation, the expressio
93 However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred
97 A computed energy-minimized structure for atovaquone liganded to the yeast bc1 complex suggests th
98 oelii; these mutants exhibited resistance to atovaquone-mediated collapse of mitochondrial membrane p
99 expression signature of STAT3, we discovered atovaquone (Mepron), an antimicrobial approved by the US
101 lysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions
102 roviral therapy (cART) impacted steady-state atovaquone plasma concentrations in human immunodeficien
107 (cohort 1A), six participants received daily atovaquone-proguanil 1 day before CHMI (cohort 1B), and
108 oral regimen only (95 AL, 162 mefloquine, 36 atovaquone-proguanil [AP], and 17 others), and 87 were a
109 M265 1 day before CHMI and six of six in the atovaquone-proguanil cohort were protected, whereas plac
110 Indonesia or Papua New Guinea, in which case atovaquone-proguanil is best, with mefloquine or quinine
113 ble-blind trial to establish the efficacy of atovaquone-proguanil to prevent malaria with the goal of
114 iaquine, atovaquone-proguanil, or artesunate-atovaquone-proguanil treatment groups and followed for 2
119 randomly assigned to artesunate-amodiaquine, atovaquone-proguanil, or artesunate-atovaquone-proguanil
124 ochrome b genes from 2 of 4 patients who had atovaquone prophylaxis failure contained mutations resul
128 dertaking clinical studies to assess whether atovaquone reduces tumour hypoxia in patients, thereby i
130 f this class to overcome parasite Q(o)-based atovaquone resistance and provides critical structural i
133 To better understand the molecular basis of atovaquone resistance, we have introduced seven of the m
138 To that end, we derived nine independent atovaquone-resistant malaria parasite lines by suboptima
139 have introduced seven of the mutations from atovaquone-resistant P. jirovecii into the cytochrome b
140 levels of expression, compared with the 3D7 (atovaquone-sensitive) control strain in bc(1) and cytoch
143 parasites rendered the complex resistant to atovaquone, thereby providing direct proof that the muta
149 ases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence inte
152 50% growth inhibition, while the IC(50) for atovaquone (which does not inhibit FPPS) remained the sa
153 shift of the inhibitory constant (K(i)) for atovaquone with a concomitant reduction in the V(max) of
154 ogates to model the molecular interaction of atovaquone with human and resistant pathogen enzymes.
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